Correlation of Mismatch Repair Deficiency with Clinicopathological Features and Programmed Death-Ligand 1 Expression in Thyroid Carcinoma

Background Mutations in DNA mismatch repair (MMR) genes associated with thyroid carcinoma (TC) have rarely been reported, especially in East Asian populations. Methods We examined tumor tissue from a cohort of 241 patients diagnosed with TC between 2008 and 2020. MMR proteins were detected using tissue microarray-based immunohistochemistry in order to identify MMR-protein-deficient (MMR-D) and MMR-protein-intact (MMR-I) tumors. We retrospectively summarized the clinicopathologic characteristics of patients with MMR-D TC, measured the expression of PD-L1, and recorded overall survival (OS) and other clinical outcomes. Results In our cohort, there were 18 (7.5%) MMR-D (MLH1, MSH2, MSH6, and PMS2) patients, including 12 with papillary TC (PTC) (6.7%), 2 with poorly differentiated TC (PDTC) (4.7%), and 4 with anaplastic TC (ATC) (22.2%). Half of them (9/18) showed a specific deletion in MSH6, and 6 of them also carried variants in the MSH6 and PMS2 gene. Survival was significantly better in patients with MMR-D ATC than in those with MMR-I tumors (p=0.033). Four of the 18 MMR-D patients (22%) were found to be PD-L1 positive. Their OS was much shorter than that of PD-L1-negative patients. Conclusions MMR-D and PD-L1 positivity appear to be associated with clinicopathological characteristics and prognosis in TC. The results indicate that MMR status may have important prognostic significance in TC. Therefore, immune checkpoint inhibitors that target the PD-1/PD-L1 pathway may be a treatment option for TCs.

Total Protein–Chloride Ratio in Pleural Fluid Independently Predicts Overall Survival in Malignant Pleural Effusion at the First Diagnosis

ObjectivePre-treatment biomarkers to estimate overall survival (OS) for malignant pleural effusion (MPE) are unidentified, especially those in pleural fluid. We evaluated the relationship between OS and total protein–chloride ratio in malignant pleural effusion (PE TPClR).Materials and MethodsA retrospective study was undertaken to identify patients from 2006 to 2018 who had pathologically or cytologically confirmed MPE and received no tumor-targeted therapy. We recorded the pre-treatment clinicopathologic characteristics and follow-up status. OS was estimated by the Kaplan–Meier method, and the association between variables and OS was evaluated by Cox proportional hazards models.ResultsWe screened 214 patients who met the eligibility criteria. The optimal cutoff value for the PE TPClR was set at 0.53. The univariate analysis showed that there was a significant correlation between PE TPClR and OS (P < 0.001). The multivariate analysis between OS and the variables selected from the univariate analysis showed that the levels of neutrophil, alkaline phosphatase, neuron-specific enolase, platelets, albumin in peripheral blood, and white blood cells in pleural effusion were also independent predictors of OS.ConclusionIn patients with MPE, pre-treatment PE TPClR independently predicts OS. Although further research is necessary to generalize our results, this information will help clinicians and patients to determine the most appropriate treatment for MPE patients.

Prognostic and Clinicopathologic Significance of Neutrophil-to-Lymphocyte Ratio in Esophageal Cancer: An Update Meta-Analysis

Background: Esophageal cancer is one of the most common cancers with significant morbidity and mortality. It is important to predict the prognosis of patients. The purpose of this study was to comprehensively assess the prognostic and clinicopathologic significance of NLR in patients with esophageal cancer. Methods: A systematic literature search was performed using PubMed, Cochrane Library, Embase, Web of Science, MEDLINE, and CNKI. This meta-analysis was conducted in accordance with PRISMA guidelines. Hazard ratio (HR) with 95% confidence interval (CI) was used as the effect estimation to evaluate the prognostic role of NLR. Odds ratio (OR) was used to evaluate the relation between NLR and clinicopathologic characteristics. Results: A total of 8431 patients from 32 studies were included in this meta-analysis. The pooled results showed that elevated NLR might predict poor prognosis: The factors considered included overall survival (OS) (HR, 1.57; 95% CI, 1.40-1.75; P < .001), cancer-specific survival (CSS) (HR, 1.28; 95% CI, 1.09-1.49; P < .001), progression-free survival (PFS) (HR, 1.45; 95% CI, 1.29-1.72; P < .001), and disease-free survival (DFS) (HR,1.58; 95% CI, 1.27-1.97; P < .001). High NLR was also associated with tumor differentiation, tumor length, tumor invasion depth, lymph node metastasis, and clinical stage. No significant association was observed between NLR and metastasis stage (OR, 1.69; 95% CI, 0.98-2.98; P = .058). Conclusions: The results of this meta-analysis suggest that elevated NLR value might predict poor prognosis (OS, CSS, PFS, and DFS), according to abnormal clinicopathologic parameters.

Clinical significance of additional gastrectomy after non-curative endoscopic submucosal dissection for early gastric cancer: a retrospective single-center study

Purpose: Additional surgery is recommended for patients after a non-curative endoscopic submucosal dissection (ESD) to prevent residual cancer (RC) or lymph node metastasis (LNM). We aimed to evaluate the clinicopathologic characteristics of patients who underwent an additional gastrectomy after a non-curative ESD procedure and identify the risk factors of RC and LNM.Methods: We retrospectively assessed the clinicopathological factors of 73 patients who underwent additional gastrectomy following a non-curative ESD between January 2009 and December 2019 at our center.Results: RC and LNM rates after additional gastrectomy were 9.6% and 8.2%, respectively. Invasion deeper than 500 μm (P = 0.045), positive horizontal resection margin (P < 0.001), and positive ESD margin (P = 0.001) were identified as statistically significant factors in univariate analysis for RC, but not in multivariate analysis. Lymphatic invasion was the only risk factor found to be significant in both univariate and multivariate analyses (P = 0.005 and P = 0.012).Conclusion: Additional gastrectomy is necessary to prevent RC or LNM after non-curative ESD. Lymphatic invasion was also associated with LNM in patients who underwent an additional gastrectomy after a non-curative ESD, and in such cases, active treatment is required.

Chemoradiotherapy is an Alternative Choice for Patients with Primary Mediastinal Seminoma

Background: The low incidence of primary mediastinal seminomas has precluded the development of clinical trials on mediastinal seminomas. We investigated the clinicopathologic characteristics, prognosis of patients with primary mediastinal seminomas as well as the efficiency of nonsurgical treatments compared with treatments containing surgery.Methods: We retrospectively collected data on the clinicopathologic characteristics, treatments, toxicities, and survival of 27 patients from a single center between 2000 and 2018. Patients were divided into two groups according to whether they received operation. Survivals were assessed using the Kaplan-Meier method. Univariate analysis was performed using the log-rank test.Results: The median age was 28 (13-63) years. The most common symptoms were chest pain (29.6%), cough (25.9%), and dyspnea (22.2%). There were 13 and 14 patients in surgery and non-surgery group. Patients in the non-surgical group were more likely to be with poor performance scores (100% vs.76.9%) and disease invaded to adjacent structures(100% vs.76.9%) especially great vessels(100% vs.46.2%).The median follow-up period was 32.23 (2.7-198.2) months. There was no significant difference of overall survival (5-year 100% vs 100%), cancer-specific survival (5-year 100% vs.100%), local regional survival (5-year 91.7% vs.90.0%, p=0.948) , distant metastasis survival (5-year 100.0% vs. 90.9%, p=0.340) and progression-free survival (82.5% vs.90.0%, p=0.245) between patients with and without surgery. Conclusions: Primary mediastinal seminoma was with favorable prognosis, even though frequently invasion into adjacent structures brings difficulties to surgery administration. Chemoradiotherapy is an alternative treatment with both efficacy and safety.

Clinicopathologic Characteristics and Outcomes of Simultaneous Multiple Primary Lung Cancer

Background. Simultaneous multiple primary lung cancer has been detected increasingly nowadays with the development of image technology. However, the clinicopathologic characteristics and outcomes are not clear. Methods. All consecutive patients diagnosed as simultaneous multiple primary lung cancer according to Martini–Melamed and American College of Chest Physicians criteria from June 2010 to June 2019 in our center were enrolled. The clinicopathologic characteristics and outcomes were compared between patients with the same histological type and different histological types. Results. A total of 336 patients were enrolled, consisting of 297 (88.4%) patients with the same histological type and 39 (11.6%) patients with different histological types. Compared to patients with the same histological type, patients with different histological types were more commonly males (87.2% vs. 34.0%; p < 0.001 ) with an older age (65 [62–69] vs. 59 [52–65] yrs; p < 0.001 ) at diagnosis. Also, patients with different histological types showed worse respiratory function and more advanced stage according to TNM staging. The 1-, 2-, and 3-year overall survival of overall patients was 97.7%, 96.1%, and 92.2%, and the 1-, 2-, and 3-year recurrence-free survival of overall patients was 96.8%, 92.9% and 85.7%, respectively. Importantly, patients with different histological types showed worse overall survival ( p < 0.001 ) and recurrence-free survival ( p = 0.002 ) than patients with same histological type. The multivariable Cox proportional hazard model revealed that presence of different histological types was significant predictor for worse overall survival (adjusted hazard ratio: 10.00; 95% confidence interval: 2.92–34.48; p < 0.001 ) and recurrence-free survival (adjusted hazard ratio: 2.59; 95% confidence interval: 1.14–5.88; p = 0.023 ). Conclusions. Although relatively less common in simultaneous multiple primary lung cancer, patients with different histological types showed worse clinical characteristics and outcomes.

Clinicopathologic characteristics, therapeutic modalities and survival outcomes of plasmablastic lymphoma: A real-world study

IntroductionPlasmablastic lymphoma(PBL)，an extremely rare subtype of B-cell non-Hodgkin lymphoma, is characterized by aggressiveness, rapid progression and bleak prognosis. Neither standardized regimen nor consensus for PBL treatment has been established.Material and methodsWe retrospectively analyzed the clinicopathologic characteristics, therapeutic modalities and survival outcomes of 418 patients registered in the Surveillance, Epidemiology, and End Results (SEER) database from 2008 to 2016 and 21 (19 treated) patients in our institution. Kaplan-Meier survival curves and log-rank test for overall survival and disease-specific survival were performed to compare each variable. Variables with statistical significance in the univariate Cox regression were incorporated into the multivariate model to determine the independent prognostic factors.ResultsIn patient cohort from SEER, PBL has a striking male predilection. The median OS for all PBL patients was 17 months. The 1-year,3-year and 5-year OS rate were 54.4%, 40.4% and 37.2% respectively.Chemotherapy alone or chemotherapy combined with radiotherapy could significantly reduce the risk of death and extend the patients’ survival, yielding HR of 0.209(95%CI 0.152-0.288) and 0.187(95%CI 0.089-0.394), respectively. Radiation alone seemed useless. All patients from our institution were HIV-negative. The main therapeutic regimens were CHOP or CHOPE, DA-EPOCH, DHAP and ESHAP. Complete response was achieved in only 3 patients, while partial response in 10 patients. The median OS was 7 months. Fourteen patients later died of the disease progression.ConclusionsPrevious malignancy history, Ann Arbor stage and therapeutic modality were independent prognostic factors. Bortezomib combined with DA-EPOCH may serve as an effective regimen for PBL. The optimal therapeutic modality necessitates further exploration.

PDGFRB is a potential prognostic biomarker and correlated with immune infiltrates in gastric cancer

Gastric cancer (GC) is a common cancer with high mortality and morbidity rates worldwide. Although medical and surgical treatments have improved, the mechanisms of the progression of GC remain unclear. Platelet-derived growth factor receptor-β (PDGFRB) plays a pivotal role in angiogenesis and tumor cell proliferation and has been suggested as a prognostic marker of cancer. This study aimed to explore the relationship of PDGFRB expression with clinicopathologic characteristics, immune cell infiltration status, and prognosis in GC. In this study, we visualized the expression and prognostic values of PDGFRB in GC using the Oncomine, UALCAN, GEPIA, and Kaplan-Meier Plotter databases. And then we explored the potential relationships between PDGFRB expression and the levels of immune cell infiltration using the TIMER, GEPIA databases and CIBERSORT algorithm. Furthermore, LinkedOmics analysis was performed to explore the functions for PDGFRB. The results showed close correlations between PDGFRB and immune cell infiltration especially M2 Macrophage infiltration in GC. High PDGFRB expression was related to poor outcomes in GC. High PDGFRB expression can negatively affect GC prognosis by promoting angiogenesis and modulating the tumor immune microenvironment. These results strongly suggest that PDGFRB can be used as a prognostic biomarker of GC and provide novel insights into possible immunotherapeutic targets.

Oncocytic Papillary Thyroid Carcinoma and Oncocytic Poorly Differentiated Thyroid Carcinoma: Clinical Features, Uptake, and Response to Radioactive Iodine Therapy, and Outcome

ObjectiveThe main objective of this study was to review the clinicopathologic characteristics and outcome of patients with oncocytic papillary thyroid carcinoma (PTC) and oncocytic poorly differentiated thyroid carcinoma (PDTC). The secondary objective was to evaluate the prevalence and outcomes of RAI use in this population.MethodsPatients with oncocytic PTC and PDTC who were treated at a quaternary cancer centre between 2002 and 2017 were retrospectively identified from an institutional database. All patients had an expert pathology review to ensure consistent reporting and definition. The cumulative incidence function was used to analyse locoregional failure (LRF) and distant metastasis (DM) rates. Univariable analysis (UVA) was used to assess clinical predictors of outcome.ResultsIn total, 263 patients were included (PTC [n=218], PDTC [n=45]) with a median follow up of 4.4 years (range: 0 = 26.7 years). Patients with oncocytic PTC had a 5/10-year incidence of LRF and DM, respectively, of 2.7%/5.6% and 3.4%/4.5%. On UVA, there was an increased risk of DM in PTC tumors with widely invasive growth (HR 17.1; p&lt;0.001), extra-thyroidal extension (HR 24.95; p&lt;0.001), angioinvasion (HR 32.58; p=0.002), focal dedifferentiation (HR 19.57, p&lt;0.001), and focal hobnail cell change (HR 8.67, p=0.042). There was additionally an increased risk of DM seen in male PTC patients (HR 5.5, p=0.03).The use of RAI was more common in patients with larger tumors, angioinvasion, and widely invasive disease. RAI was also used in the management of DM and 43% of patients with oncocytic PTC had RAI-avid metastatic disease. Patients with oncocytic PDTC had a higher rate of 5/10-year incidence of LRF and DM (21.4%/45.4%; 11.4%/40.4%, respectively). Patients with extra-thyroidal extension had an increased risk of DM (HR 5.52, p=0.023) as did those with angioinvasion. Of the patients with oncocytic PDTC who received RAI for the treatment of DM, 40% had RAI-avid disease.ConclusionWe present a large homogenous cohort of patients with oncocytic PTC and PDTC, with consistent pathologic reporting and definition. Patients with oncocytic PTC have excellent clinical outcomes and similar risk factors for recurrence as their non-oncocytic counterparts (angioinvasion, large tumor size, extra-thyroidal extension, and focal dedifferentiation). Compared with oncocytic PTCs, the adverse biology of oncocytic PDTCs is supported with increased frequency of DM and lower uptake of RAI.